title: Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodelling: the TIPTOP trial.
abstract: OBJECTIVE
  Experimental studies suggest that doxycycline attenuates post-infarction remodelling and exerts protective effects on myocardial ischaemia/reperfusion injury. However, the effects of the drug in the clinical setting are unknown. The aim of this study was to examine the effect of doxycycline on left ventricular (LV) remodelling in patients with acute ST-segment elevation myocardial infarction (STEMI) and LV dysfunction.
  
  
  RESULTS
  Open-label, randomized, phase II trial. Immediately after primary percutaneous coronary intervention, patients with STEMI and LV ejection fraction < 40% were randomly assigned to doxycycline (100 mg b.i.d. for 7 days) in addition to standard therapy, or to standard care. The echo LV end-diastolic volumes index (LVEDVi) was determined at baseline and 6 months. (99m)Tc-Sestamibi-single-photon emission computed tomography infarct size and severity were assessed at 6 months. We calculated a sample size of 110 patients, assuming that doxycycline may reduce the increase in the LVEDVi from baseline to 6 months > 50% compared with the standard therapy (statistical power > 80% with a type I error = 0.05). The 6-month changes in %LVEDVi were significant smaller in the doxycycline group than in the control group [0.4% (IQR: -16.0 to 14.2%) vs.13.4% (IQR: -7.9 to 29.3%); P = 0.012], as well as infarct size [5.5% (IQR: 0 to 18.8%) vs. 10.4% (IQR: 0.3 to 29.9%) P = 0.052], and infarct severity [0.53 (IQR: 0.43-0.62) vs. 0.44 (IQR: 0.29-0.60), P = 0.014], respectively.
  
  
  CONCLUSIONS
  In patients with acute STEMI and LV dysfunction, doxycycline reduces the adverse LV remodelling for comparable definite myocardial infarct size (NCT00469261).
authors.affiliation: Division of Cardiology, University of Florence, Careggi Hospital, Largo Brambilla 3, Florence I-50141, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Cerisano
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Buonamici
authors.forename: Renato
authors.initials: R
authors.lastname: Valenti
authors.forename: Roberto
authors.initials: R
authors.lastname: Sciagrà
authors.forename: Silvia
authors.initials: S
authors.lastname: Raspanti
authors.forename: Alberto
authors.initials: A
authors.lastname: Santini
authors.forename: Nazario
authors.initials: N
authors.lastname: Carrabba
authors.forename: Emilio Vincenzo
authors.initials: EV
authors.lastname: Dovellini
authors.forename: Roberta
authors.initials: R
authors.lastname: Romito
authors.forename: Alberto
authors.initials: A
authors.lastname: Pupi
authors.forename: Paolo
authors.initials: P
authors.lastname: Colonna
authors.forename: David
authors.initials: D
authors.lastname: Antoniucci
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D017023:Coronary Angiography; D018450:Disease Progression; D004318:Doxycycline / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004452:Echocardiography; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D062645:Percutaneous Coronary Intervention; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; D004318:Doxycycline
keywords: Echocardiography; Myocardial infarction; Remodelling